CN112420479A

CN112420479A - Miniature mass spectrometer

Info

Publication number: CN112420479A
Application number: CN202011278051.2A
Authority: CN
Inventors: 吴焕铭
Original assignee: Ningbo University
Current assignee: Ningbo University
Priority date: 2020-11-16
Filing date: 2020-11-16
Publication date: 2021-02-26
Anticipated expiration: 2040-11-16
Also published as: CN112420479B

Abstract

The invention discloses a miniature mass spectrometer, which specifically comprises: an ionization source for converting sample molecules into gas phase ions within a region substantially at atmospheric pressure; a trapping device for trapping and storing ions; a discontinuous atmospheric pressure interface means for transporting ions from said region at substantially atmospheric pressure to at least one other region of reduced pressure, wherein said atmospheric pressure interface means comprises a valve for controlling entry or cessation of ions into said trapping means, said valve being opened a plurality of times to transport ions into said trapping means in a discontinuous manner to trap and concentrate ions; the device also comprises a mass analyzer, a detector, a circuit, a vacuum cavity, a vacuum pump, a barometer and a computer. The invention provides a miniature mass spectrometer which can improve the sensitivity and ion detection limit and improve the stability of ion intensity.

Description

Miniature mass spectrometer

Technical Field

The invention relates to the field of miniature mass spectrometers, in particular to an ion leading-in device of a miniature mass spectrometer with a discontinuous atmospheric pressure interface.

Background

The miniature mass spectrometer is widely applied in some scenes with on-site real-time analysis requirements, and typical application scenes comprise industrial wastewater monitoring, chemical warfare agent detection, pesticide and veterinary drug residue detection in food, clinical diagnosis and the like.

The Atmospheric Pressure Interface (API) of the mass spectrometer is used to transport ions from the atmospheric (atmospheric) region to the low-pressure region of the vacuum chamber. The application of the API makes miniature mass spectrometers a unique advantage over laboratory mass spectrometers in the field application scenario, as the API allows the mass spectrometer to use multiple ion sources operating at atmospheric pressure, thereby simplifying the pre-processing and ionization processes of the sample. A typical atmospheric pressure ion source includes: electrospray ion source (ESI) (Yamashita M, Fenn JB. Electron emission source, analysis on The free-jet The. The Journal of Physical chemistry, 1984;88(20): 4451-9.), Atmospheric Pressure ion source (APCI) (Carroll DI, Dzidic I, Stillwell RN, Haegele KD, Horn EC. Atmos compressive characterization emission method, Mass analysis system, analysis chemistry 1975;47(14) (2369-73) Laser Desorption source in a liquid chromatography-Mass analysis system, Matrix Analysis (MALDI) (Lawsonia analysis, Mass analysis, S.I. M.S. 2000, gradient analysis, S.S. 5;47(14) Electrospray ion source, Mass analysis, S.S. 5; Mass analysis, MS.S. 73; Mass analysis, S.S. 5, gradient analysis, S.S. 5, Mass analysis, MS, S.S. 5, and S.S. 5 (MS; Mass analysis, S.S. 5, MS, Mass analysis, S. 5, MS, S. analysis, S. 5, MS, S. 2, cooks RG. Mass mapping under atmospheric conditions with resolution electronics Science (New York, NY) 2004;306(5695): 471-3.) Ion Source (DART) was directly analyzed in real time (code RB, Laram ie JA, Durst HD. Versatile New Ion Source for the Analysis of Materials in Open Air interface under Ammonia Conditioning chemistry 2005 (228): 2297. 302.), atmospheric pressure medium Barrier Discharge (DBDI) (Na N, Zha M, Zhang S, Yang C, Zhang X. Development of a Dielectric Barrier Ion Source for Mass Spectrometry of Mass Spectrometry 18. Mass Spectrometry of FIGS. 18. moisture of FIGS. 10. 1. 4. and so on.

The current typical laboratory bench top mass spectrometer of the API architecture is continuously fed, and ions generated at atmospheric pressure are introduced into a vacuum chamber through a normally open channel comprising a continuous differential pumping stage. The continuous differential pump stage transfers ions to the first stage of the vacuum cavity through the capillary with small inner diameter, and then the ions are guided into the second stage of the vacuum cavity and the subsequent more stages of the vacuum cavity through the sampling cone. The first stage region is typically pumped to a pressure of about 1 torr (torr) using a primary pump such as a diaphragm pump, scroll pump, etc., and the second and subsequent stages are pumped to a pressure of 10 torr using a single or multiple turbomolecular pumps^-5Below for ion manipulation and mass divisionAnd (6) analyzing. In the ion introduction process of the API structure mass spectrometer, ions with 2 orders of magnitude and 1 order of magnitude can be lost in the first stage and the second stage respectively, and the total ion transmission efficiency of the API structure mass spectrometer with continuous sample introduction is lower than 0.1%. Ion transport efficiency can often be improved by increasing the sampling cone between stages, but a pump with a higher pumping speed is required to maintain the required vacuum. By replacing the sampling cone with an ion funnel, focusing and directing ions into the second stage at a higher pressure, the efficiency of ion transport through the second stage can be successfully increased by a factor of 10.

When the API structure is applied to a small mass spectrometer, a pump having a smaller pumping speed must be used due to the demands for volume, weight, and power consumption, but this results in further reduction in ion transport efficiency. A compact mass spectrometer is realized by using a vacuum system with a continuous feed API structure and a two-stage differential structure, wherein an ion funnel is used for transmitting ions in a first stage vacuum cavity, and a linear ion trap is used for mass analysis in a second stage vacuum cavity, wherein a molecular pump adopts a pumping speed of 80L/s to maintain a required air pressure (ZHai Y, Feng Y, Wei Y, Wang Y, Xu W. Development of a miniature mass spectrometer with continuous atomic pressure expression interface. analysis. 2015;140(10): 3406-14.). The advent of discontinuous sampling API architecture, namely DAPI (discontinuous atmospheric pressure interface), has enabled smaller mass spectrometers to use pumps with lower pumping speeds (11L/s molecular pumps) while maintaining ion transport efficiencies comparable to continuous sampling APIs. Because high vacuum is required in the vacuum chamber only during mass analysis, and high vacuum is not required in the processes of ion introduction and ion cooling capture, the mass spectrometer with the continuous sample introduction API structure does not fully utilize the efficiency of the pump. The core idea of the DAPI structure is to make full use of the pump efficiency, and periodically open the sample channel to make ions enter the vacuum chamber under high-speed airflow, and then close the channel and wait for the vacuum chamber to be pumped to the air pressure required for mass analysis for ion scanning (Liang, R Graham C, Zheng o. Breaking the pumping and transporting barrier in mass spectrometry. Analytical chemistry. 2008;80(11): 4026-32.). The DAPI structure controls the introduction of ions by controlling the opening and closing of a tube (typically a silicone tube) through a valve (typically a pinch valve) (CN 101820979A, a patent entitled discontinuous atmospheric pressure interface). Compared with the continuous feeding API structure, the volume and the weight of the mass spectrometer can be further reduced by using the DAPI structure.

Although the volume and weight of the mass spectrometer can be reduced by the DAPI structure under the condition of ensuring certain ion transmission efficiency, compared with the mass spectrometer with the API structure with continuous feeding, the total ions entering the mass analyzer are still less, so that the sensitivity and the detection limit of the mass spectrometer with the DAPI structure are not as good as those of a small-sized mass spectrometer with the API structure with continuous feeding. The continuous feed API structure can increase the total ions entering the mass analyzer by extending the ion introduction time, thereby increasing the sensitivity and detection limit of the instrument. However, the ion introduction time of a small mass spectrometer of DAPI structure cannot be arbitrarily extended. Since the gas pressure in the vacuum chamber rises rapidly once the pinch valve is opened to introduce ions, the opening time of the pinch valve cannot be extended indefinitely to maintain the minimum gas pressure required by the ion trap plasma trapping device during the ion cooling phase and the minimum gas pressure required by the turbomolecular pump to operate normally, resulting in a limited total number of ions entering the mass analyzer during the valve opening phase, further limiting the sensitivity and detection limits of the DAPI-structured compact mass spectrometer. In addition, after the pinch valve is opened, ions enter the vacuum chamber with the high velocity Gas Flow, which negatively affects the Mass stability of the Mass analysis and the stability of the ion peak intensity (Huo X, Zhu X, Tang F, Zhang J, Zhang X, Yu Q, et al, discrete surface preparation the Gas Flow Effects on Miniature CAPI Mass Spectrometry. Analytical chemistry. 2020;92(5): 3707-15.).

Therefore, there is a need for a device that can improve the efficiency of iontophoresis of DAPI structures in small mass spectrometers.

Disclosure of Invention

In order to solve the defects in the prior art, the invention provides the miniature mass spectrometer which can improve the sensitivity and the detection limit and improve the stability of the ionic strength.

The technical scheme adopted by the invention for solving the technical problems is as follows: a miniature mass spectrometer comprising:

an ionization source for converting sample molecules into gas phase ions within a region substantially at atmospheric pressure;

a trapping device for trapping and storing ions;

a discontinuous atmospheric pressure interface means for transporting ions from said region at substantially atmospheric pressure to at least one other region of reduced pressure, wherein said atmospheric pressure interface means comprises a valve for controlling entry or cessation of ions into said trapping means, said valve being opened a plurality of times to transport ions into said trapping means in a discontinuous manner to trap and concentrate ions;

a mass analyzer in cascade with the trapping device for manipulating ions therein to exit in mass order;

a detector for converting the ions into an electrical signal;

circuitry for providing electrical signals required for operation of the apparatus including the capture means and the mass analyser;

a vacuum chamber for housing one or more devices including the capture device, the mass analyzer, and the detector that are required to operate in a sub-atmospheric pressure environment;

the vacuum pump is used for pumping the air pressure in the vacuum cavity to be lower than the atmospheric pressure;

a barometer for monitoring the pressure within the vacuum chamber;

a computer for processing the electrical signal data.

In some embodiments, a mass spectrometry timing is controlled by the circuitry, the mass spectrometry timing for a cycle being as follows: a first stage in which the valve is closed and the capture device, the mass analyser and the detector are inoperative; in the second stage, the valve is opened and closed for multiple times, ions are guided to enter the capture device repeatedly and discontinuously, at the moment, the capture device works to capture and enrich the ions, and the mass analyzer and the detector do not work; a third stage in which the valve is held closed and ions trapped and enriched in the trapping device are transferred to the mass analyser, the mass analyser and the detector operating to obtain an electrical signal reflecting mass spectral data; and in the fourth stage, the electric signal is processed by the circuit and then transmitted to the computer, and data processing is carried out by software to obtain a mass spectrogram. Therefore, compared with the traditional mass spectrometer with a discontinuous atmospheric pressure interface, the invention does not increase any circuit hardware and mechanical structure, only needs to change the circuit control time sequence, but obtains the improvement of the sensitivity and the detection limit of the miniature mass spectrometer due to the ion enrichment function of the capturing device.

Wherein the time length of each opening of the valve meets the following conditions: and ensuring that the maximum air pressure monitored by the barometer is within the air pressure range of normal work of the capturing device and the vacuum pump. The atmospheric pressure is monitored by a barometer, the opening time of each valve is controlled, and the opening time of the valve cannot be overlong, so that the maximum atmospheric pressure is ensured to be within the atmospheric pressure range in which a capture device and a vacuum pump (especially a molecular pump) can normally work; the valve opening time should not be too short to ensure that enough ions enter the trapping device each time the valve is opened.

In some embodiments, the ionization source employs any one of: electrospray ionization, nano-spray ionization, atmospheric pressure matrix-assisted laser desorption ionization, atmospheric pressure chemical ionization, desorption electrospray ionization, real-time direct analysis ionization, atmospheric pressure dielectric barrier discharge ionization, atmospheric pressure low-temperature plasma desorption ionization and electrospray-assisted laser desorption ionization.

In some embodiments, the discontinuous atmospheric pressure interface device further comprises: the pipe is arranged in the valve, the valve is clamped in the middle of the pipe, the first capillary is inserted into the first end of the pipe, the second capillary is inserted into the second end of the pipe, the first capillary and the second capillary are not overlapped with the part clamped by the pipe and the valve, the first capillary is communicated with the atmospheric pressure, and the second capillary is connected with the inlet of the capture device.

In some embodiments, the valve is selected from a pinch valve, a needle valve, a flapper valve; the pipe is made of an inert rubber material, the inert rubber material comprises silicon rubber, conductive rubber and anti-static rubber, and the doped material of the conductive rubber and the anti-static rubber is carbon or other conductive metals; the first capillary tube and the second capillary tube are both made of inert metal materials, and the outer diameters of the first capillary tube and the second capillary tube are slightly larger than the inner diameter of the tubes so as to ensure air tightness.

In some embodiments, the trapping device is an ion storage device of a mass spectrometer or a mass analyzer with ion trapping capabilities.

In some embodiments, the ion storage device is selected from an ion funnel or an electrostatic lens: the mass analyzer is selected from any one of a four-stage ion trap, a rectangular ion trap, a cylindrical ion trap, an ion cyclotron resonance trap and an orbit trap.

In some embodiments, the capture device and the mass analyzer are placed within the same vacuum cavity or within two cascaded vacuum cavities, respectively. When the trapping device and the mass analyzer are in a cascade mode, ions are enriched by the trapping device firstly, and then enter the mass analyzer through the guiding device for further analysis.

In some embodiments, an ion guide device for guiding ions from the trapping device into the mass analyzer is further disposed between the two cascaded vacuum chambers, the ion guide device being selected from a sampling cone or an ion guide rod.

In some embodiments, the detector is selected from the group consisting of an electron multiplier tube, a faraday cup, a photomultiplier tube, a microchannel plate; the barometer is selected from a pirani vacuum gauge, a thermocouple vacuum gauge, a hot cathode vacuum gauge, and a cold cathode vacuum gauge.

Compared with the traditional mass spectrometer with a discontinuous atmospheric pressure interface, the mass spectrometer has the advantages that: (1) the aim of enriching ions is achieved by opening and closing the valve for multiple times and keeping the capture device working in the period, so that the sensitivity and the detection limit of the mass spectrometer are improved; (2) due to the ion enrichment effect of opening the valve for multiple times, the influence of high-speed airflow on the stability of the ion strength when the valve is opened can be reduced, so that the signal stability of the miniature mass spectrometer is improved; (3) compared with the traditional mass spectrometer with a continuous atmospheric pressure interface, the invention has the advantages that the requirement of the system on the pumping speed of the vacuum pump can be reduced by using the discontinuous atmospheric pressure interface and carrying out discontinuous sampling for many times, thereby reducing the volume, weight and power consumption of the mass spectrometer and playing an important role in carrying out on-site real-time analysis by applying a miniature portable mass spectrometer; (4) the invention does not increase or change any circuit hardware and mechanical structure of the discontinuous atmospheric pressure interface mass spectrometer, only needs to change the control time sequence to realize the device, but obtains the improvement of the sensitivity and the detection limit of the micro mass spectrometer due to the ion enrichment function of the capturing device.

Drawings

FIG. 1 is a schematic diagram of a micro mass spectrometer with an ion funnel and a Linear Ion Trap (LIT) cascade connected according to an embodiment of the present invention, wherein the ion funnel and the LIT cascade are provided with discrete atmospheric pressure interfaces;

FIG. 2 is a schematic diagram of a miniature mass spectrometer in which a Quadrupole Ion Trap (QIT) and a Linear Ion Trap (LIT) are cascaded and a discontinuous atmospheric pressure interface is adopted according to another embodiment of the invention;

FIG. 3 is a schematic structural diagram of a miniature mass spectrometer in which a Linear Ion Trap (LIT) and a Linear Ion Trap (LIT) are cascaded and a discontinuous atmospheric pressure interface is adopted according to another embodiment of the invention;

fig. 4a is a mass spectrum obtained after electrospray ionization of a 0.1ppm (one ten million) concentration enrofloxacin solution recorded when a DAPI structure mass spectrometer of the present invention is opened 1 time, wherein the ion introduction time is 5ms, and the DAPI opening interval is 350 ms;

fig. 4b is a mass spectrum obtained after electrospray ionization of the enrofloxacin solution with the concentration of 0.1ppm (one ten million) recorded when the DAPI structure mass spectrometer of the present invention is opened 5 times, wherein the ion introduction time is 5ms, and the DAPI opening interval is 350 ms;

FIG. 4c is a mass spectrum obtained after electrospray ionization of a 0.1ppm (one ten million) concentration enrofloxacin solution recorded when DAPI is opened 10 times, wherein the ion introduction time is 5ms, and the DAPI opening interval is 350 ms;

FIG. 4d is a mass spectrum obtained after electrospray ionization of a 0.1ppm (one ten million) concentration enrofloxacin solution recorded when DAPI is opened 15 times according to the present invention, wherein the ion introduction time is 5ms, and the DAPI opening interval is 350 ms;

FIG. 5a is a mass spectrum obtained after electrospray ionization of a mixed solution of 0.05ppm (five parts per million) of enoxacin and 0.05ppm (five parts per million) of reserpine recorded when DAPI of the present invention is turned on 1 time, wherein the ion introduction time is 5ms, and the DAPI turning-on interval is 350 ms;

FIG. 5b is a mass spectrum obtained after electrospray ionization of a mixed solution of 0.05ppm (five parts per million) of enoxacin and 0.05ppm (five parts per million) of reserpine recorded when DAPI of the present invention is turned on 5 times, wherein the ion introduction time is 5ms, and the DAPI turning-on interval is 350 ms;

FIG. 5c is a mass spectrum obtained after electrospray ionization of a mixed solution of 0.05ppm (five parts per million) of enoxacin and 0.05ppm (five parts per million) of reserpine recorded when the DAPI of the present invention is opened 10 times, wherein the ion introduction time is 5ms and the DAPI opening interval is 350 ms;

fig. 5d is a mass spectrum of a mixed solution of enoxacin at a concentration of 0.05ppm (five parts per million) and reserpine at a concentration of 0.05ppm (five parts per million) obtained after electrospray ionization, recorded 15 times after opening of DAPI according to the present invention, wherein the iontophoresis time is 5ms and the DAPI opening interval is 350 ms.

The device comprises a pinch valve 1, a silicone rubber tube 2, a first capillary tube 3, a second capillary tube 4, a first-stage vacuum cavity 5, a second-stage vacuum cavity 6, a sampling cone 7, a primary pump 8 and a secondary pump 9.

Detailed Description

The present invention will be described in further detail with reference to the following drawings and examples, but the present invention is not limited thereto.

A miniature mass spectrometer comprising:

a trapping device for trapping and storing ions;

a discontinuous atmospheric pressure interface means for transporting ions from a region at substantially atmospheric pressure to at least one other region of reduced pressure, wherein the atmospheric pressure interface means comprises a valve for controlling entry or cessation of ions into the trapping means, whereby ions are captured and enriched by multiple openings of the valve to transport ions into the trapping means in a discontinuous manner;

the mass analyzer is cascaded with the capture device and is used for controlling ions in the mass analyzer to leave according to the mass size sequence;

a detector for converting the ions into an electrical signal;

the device comprises a vacuum cavity, a mass analyzer, a detector and a control circuit, wherein the vacuum cavity is used for placing one or more devices including a capture device, the mass analyzer and the detector which need to work in a pressure environment lower than atmospheric pressure;

the barometer is used for monitoring the air pressure in the vacuum cavity;

and the computer is used for processing the electric signal data.

The circuit controls the mass spectrum analysis time sequence, and the mass spectrum analysis time sequence of one period comprises the following steps: in the first stage, the valve is closed, and the capture device, the mass analyzer and the detector do not work; in the second stage, the valve is opened and closed for multiple times, ions are guided to enter the capturing device repeatedly and discontinuously, at the moment, the capturing device works to capture and enrich the ions, and the mass analyzer and the detector do not work; in the third stage, the valve is kept closed, the ions captured and enriched in the capture device are transmitted to the mass analyzer, and the mass analyzer and the detector work to obtain an electric signal reflecting mass spectrum data; and in the fourth stage, the electric signal is processed by a circuit and then transmitted to a computer, and data processing is carried out by software to obtain a mass spectrogram. Therefore, compared with the traditional mass spectrometer with a discontinuous atmospheric pressure interface, the invention does not increase any circuit hardware and mechanical structure, only needs to change the circuit control time sequence, but obtains the improvement of the sensitivity and the detection limit of the miniature mass spectrometer due to the ion enrichment function of the capturing device.

The time length of each opening of the valve meets the following conditions: the maximum air pressure monitored by the barometer is ensured to be within the air pressure range of normal work of the capturing device and the vacuum pump. The atmospheric pressure is monitored by a barometer, the opening time of each valve is controlled, and the opening time of the valve cannot be overlong, so that the maximum atmospheric pressure is ensured to be within the atmospheric pressure range in which a capture device and a vacuum pump (especially a molecular pump) can normally work; the valve opening time should not be too short to ensure that enough ions enter the trapping device each time the valve is opened.

According to different detection requirements, the ionization source adopts any one of the following: electrospray ionization, nano-spray ionization, atmospheric pressure matrix-assisted laser desorption ionization, atmospheric pressure chemical ionization, desorption electrospray ionization, real-time direct analysis ionization, atmospheric pressure dielectric barrier discharge ionization, atmospheric pressure low-temperature plasma desorption ionization and electrospray-assisted laser desorption ionization.

The discontinuous atmospheric pressure interface device further comprises: the pipe is arranged in the valve, the valve is clamped in the middle of the pipe, the first capillary is inserted into the first end of the pipe, the second capillary is inserted into the second end of the pipe, the first capillary and the second capillary are not overlapped with the part clamped by the pipe and the valve, the first capillary is communicated with the atmospheric pressure, and the second capillary is connected with the inlet of the capturing device.

The valve is selected from a pinch valve, a needle valve and a baffle valve; the pipe is made of an inert rubber material, the inert rubber material comprises silicon rubber, conductive rubber and anti-static rubber, and the doped material of the conductive rubber and the anti-static rubber is carbon or other conductive metals; the first capillary and the second capillary are both made of inert metal materials, and the outer diameters of the first capillary and the second capillary are slightly larger than the inner diameter of the tubes so as to ensure air tightness.

The trapping device is an ion storage device of a mass spectrometer or a mass analyser having ion trapping capabilities.

According to different detection requirements, the ion storage device is selected from an ion funnel or an electrostatic lens: the mass analyzer is selected from any one of a four-stage ion trap, a rectangular ion trap, a cylindrical ion trap, an ion cyclotron resonance trap and an orbit trap.

The capture device and the mass analyzer are arranged in the same vacuum cavity or respectively arranged in two cascaded vacuum cavities. When the trapping device and the mass analyzer are in a cascade mode, ions are enriched by the trapping device firstly, and then enter the mass analyzer through the guiding device for further analysis.

An ion guide device for guiding ions from the trapping device to the mass analyzer is arranged between the two cascaded vacuum chambers, and the ion guide device is selected from a sampling cone or an ion guide rod.

The discontinuous atmospheric pressure interface device is coaxially arranged with the capture device and the mass analyzer, or the discontinuous atmospheric pressure interface device is eccentrically arranged with the capture device and the mass analyzer.

The detector is selected from an electron multiplier tube, a Faraday cup, a photomultiplier tube and a microchannel plate; the barometer is selected from the group consisting of a pirani gauge, a thermocouple gauge, a hot cathode gauge, and a cold cathode gauge.

For a micro mass spectrometer using a Discontinuous Atmospheric Pressure Interface (DAPI), although the volume and weight of the micro mass spectrometer can be reduced by the DAPI structure under the condition of ensuring a certain ion transmission efficiency, the total ions entering the mass analyzer are still less compared with the mass spectrometer using the API structure with continuous feeding, so that the sensitivity and the detection limit of the mass spectrometer using the DAPI structure are not as good as those of the micro mass spectrometer using the API structure with continuous feeding. The continuous feed API structure can increase the total ions entering the mass analyzer by extending the ion introduction time, thereby increasing the sensitivity and detection limit of the instrument. However, the ion introduction time of the DAPI-structured micro mass spectrometer cannot be arbitrarily extended. Since the gas pressure in the vacuum chamber rises rapidly once the pinch valve is opened to introduce ions, the opening time of the pinch valve cannot be extended indefinitely to maintain the minimum gas pressure required by the ion trap plasma capture device during the ion cooling phase and the minimum gas pressure required by the turbomolecular pump to operate normally, resulting in a limited total number of ions entering the mass analyzer during the valve opening phase, further limiting the sensitivity and detection limit of the DAPI-structured micro mass spectrometer. In addition, after the pinch valve is opened, ions can enter the vacuum cavity along with the high-speed airflow, and the high-speed airflow can cause negative influence on the quality stability of mass analysis and the stability of ion peak intensity.

The miniature mass spectrometer adopting the DAPI structure, the capture device and the mass analyzer in cascade connection can adopt the mode of opening and closing the valve in the DAPI structure for multiple times, meanwhile, the capture device is kept working, ions can be effectively enriched, and the enriched ions are transmitted to the mass analyzer to work. Compared with a traditional mass spectrometer with a DAPI structure, the miniature mass spectrometer has the advantages that the sensitivity, the detection limit, the quality stability and the ion peak intensity stability are improved; compared with the traditional mass spectrometer with a continuous sample feeding structure, the miniature mass spectrometer has the advantages that the volume, the weight and the power consumption of the mass spectrometer can be obviously reduced because the miniature mass spectrometer adopts a DAPI structure and a vacuum pump with a lower pumping speed.

Example 1

A typical embodiment of the miniature mass spectrometer of the present invention is a mass spectrometer employing a DAPI two-stage differential pump structure, as shown in fig. 1, using a valve 1 to open and close the passage of a silicone rubber tube 2 communicating atmospheric pressure with a vacuum region. A normally closed pinch Valve (P045 a103L0a00F1, ASCO Valve inc., Florham Park, NJ) was used to control the introduction and shut-off of ions. The first capillary 3 (stainless steel capillary) connected to the atmospheric pressure had an inner diameter of 0.5mm (mm), an outer diameter of 1.6mm (1/16 '', 1/16 inches), and a length of 5cm (cm). The second capillary 4 (stainless steel capillary) connected to the vacuum chamber had an inner diameter of 1mm (mm), an outer diameter of 1.6mm (1/16 '', 1/16 inches), and a length of 5cm (cm). Both stainless steel capillary tubes are grounded. The silicone rubber tube 2 is made of a carbon-doped conductive silicone rubber tube having an inner diameter of 1.3mm (mm), an outer diameter of 3.2mm (1/8 '', 1/8 inches), and a length of 3cm (cm). Ions are in the first-stage vacuum chamber 5And the funnel can realize the trapping and the enrichment of ions during the process of opening and closing the pinch valve for multiple times. Within the second stage vacuum chamber 6 is a Linear Ion Trap (LIT) which is responsible for mass analysis of the trapped and concentrated ions. And applying direct current voltage to the end electrodes at two ends of the linear ion trap respectively to control the leading-in and storage of ions. A sampling cone 7 is arranged between the first-stage vacuum cavity and the second-stage vacuum cavity, and the aperture is 0.2mm (millimeter). The volumes of the first-stage vacuum chamber 5 and the second-stage vacuum chamber 6 were about 300cm, respectively³(cubic centimeter) and about 200cm³(cubic centimeters). The primary pump 8 is a diaphragm pump with a pumping speed of 4L/min (MVP 003-2, Pfeiffer Vacuum, Germany), the secondary pump 9 is a turbo-molecular pump with a pumping speed of 10L/s (HiPace 10, Pfeiffer Vacuum, Germany), and the secondary Vacuum chamber 6 is capable of pumping to a minimum of 2X 10^- ⁵The Torr is less. The electron multiplier Em (Model 382, Detector Technology, Inc.) is responsible for collecting the ion current signal and the vacuum gauge (MKS 925C, MKS Instruments, Inc. Wilmington, MA) is responsible for monitoring the air pressure value.

A complete mass spectrometry sequence using a miniature mass spectrometer is typically (but not limited to): and (4) introducing and cooling ions for multiple times, enriching and scanning by radio frequency. In the first stage, in the process of continuously ionizing the atmospheric pressure ion source to generate ions, a circuit controls to apply 24VDC (direct current) to the pinch valve 1, a DAPI channel is opened, the duration of the voltage applied to the pinch valve is typically several milliseconds to tens of milliseconds, and the maximum air pressure is ensured to be the air pressure at which the primary pump 8 and the secondary pump 9 can normally work, particularly the secondary turbo-molecular pump; then the circuit controls the power-down of the pinch valve 1, and the DAPI channel is closed; waiting for a period of time until the air pressure is reduced to an appropriate air pressure value again, performing experiments to obtain an optimal value of about 1mTorr, reapplying 24VDC to open the pinch valve, and repeating the steps in a circulating manner to open the pinch valve for multiple times. Applying a radio frequency voltage to the ion funnel from the first time when the pinch valve is opened, applying appropriate direct current voltages to the first and last electrodes of the ion funnel to cool and capture the introduced ions, and maintaining the radio frequency voltage applied during the multiple opening and closing of the pinch valve 1 so that the ion funnel can continuously capture and enrich the ionsDuring the period that the valve 1 is opened and closed for multiple times, no voltage is applied to the linear ion trap and the electron multiplier tube in the second-stage vacuum cavity 6; the second stage, when the pinch valve 1 is closed for the last time and the air pressure is reduced to the proper air pressure again, the experiment selects the air pressure lower than 2 multiplied by 10^-5Torr is used for obtaining better mass resolution, axial direct current voltage is applied to each electrode of an ion funnel, ions are guided into a linear ion trap in a second-stage vacuum cavity from a sampling cone, radio frequency voltage is applied to the linear ion trap and used for capturing the ions, an electrode I at the end of the linear ion trap close to the sampling cone is grounded, a direct current voltage of 300VDC is applied to an electrode II at the end of the linear ion trap far away from the sampling cone to offset axial ion kinetic energy and help the linear ion trap to cool and capture the ions, the duration of the ion guiding and cooling process is several milliseconds, no voltage is applied to an electron multiplier tube during the period, and a pinch valve is kept closed; in the third stage, a radio frequency scanning voltage and an alternating current resonance excitation voltage are applied to the linear ion trap to realize mass scanning, the same 300VDC direct current voltage is loaded on the two end electrodes, 1300VDC direct current voltage is applied to the electron multiplier tube during the period to amplify the ion signal into a current signal, and the pinch valve is kept closed; and in the fourth stage, after scanning is finished, 300VDC direct current voltage is loaded on the end close to the sampling cone, the end electrode far away from the sampling cone is grounded, residual ions are discharged, all the loading voltages on the electron multiplier tube, the linear ion trap and the ion funnel are closed, and a complete mass spectrometry period is finished.

The ion funnel in the first-stage vacuum chamber 5 of the mass spectrometer in the above embodiment can be replaced with a Quadrupole Ion Trap (QIT), and others remain unchanged, as shown in fig. 2, and the operation timing is also different from that of the above embodiment using the ion funnel, which is not described again.

The ion funnel in the first-stage vacuum chamber 5 of the mass spectrometer in the above embodiment can be replaced by a Linear Ion Trap (LIT), and the rest remains unchanged, as shown in fig. 3, and the operation timing sequence thereof is also different from that of the above embodiment using the ion funnel, and is not described again.

The linear ion trap mass analyzer in the second stage vacuum chamber of the mass spectrometer in the above embodiment may be replaced with a quadrupole, a rectangular ion trap, a cylindrical ion trap, an ion cyclotron resonance trap, an orbitrap, a time-of-flight mass analyzer, and others may remain unchanged, and the operation timing sequence is identical to that of the above embodiment except that the timing sequence of the third stage mass scan is different according to the specific mass analyzer.

In the embodiment, the mass analyzers in the second-stage vacuum cavity are all ion traps, so that tandem mass spectrometry is supported, the structure of the mass spectrometer is unchanged, and the specific time sequence is according to the tandem mass spectrometry time sequence.

Using 0.1ppm enrofloxacin solution, mixing methanol and water with a solvent of 1:1 volume ratio and 0.1% formic acid; the opening time of the pinch valve is 5ms, the opening interval is 350ms, a mass spectrogram of 1-time opening of the pinch valve is shown in fig. 4a, a mass spectrogram of 5-time opening of the pinch valve is shown in fig. 4b, a mass spectrogram of 10-time opening of the pinch valve is shown in fig. 4c, and a mass spectrogram of 15-time opening of the pinch valve is shown in fig. 4 d. The opening time of the pinch valve is 5ms, and the opening interval is 350ms, which are optimized parameters in this embodiment, and the optimized values of the opening time and the opening interval of the pinch valve are different according to different cavity sizes, pump pumping speeds, lengths and inner diameters of the first capillary and the second capillary, and detection requirements, but are included in the concept and the protection scope of the present invention.

A mixed solution of 0.05ppm (five parts per million) concentration of enoxacin and 0.05ppm (five parts per million) concentration of reserpine is used, and the solvent is methanol to water mixed with 0.1% formic acid in a volume ratio of 1: 1; the opening time of the pinch valve is 5ms, the opening interval is 350ms, fig. 5a is a mass spectrogram of 1 time opening the pinch valve, fig. 5b is a mass spectrogram of 5 times opening the pinch valve, fig. 5c is a mass spectrogram of 10 times opening the pinch valve, and fig. 5d is a mass spectrogram of 15 times opening the pinch valve.

The experimental results of fig. 4 and 5 fully illustrate that the miniature mass spectrometer of the present invention has great advantages in ion enrichment, so that the sensitivity and detection limit of the miniature mass spectrometer can be greatly improved. In addition, due to the ion enrichment effect, the influence of high-speed airflow on the stability of the ion strength when the valve is opened can be reduced, and therefore the signal stability of the miniature mass spectrometer is improved. Compared with the traditional mass spectrometer with the continuous atmospheric pressure interface, the mass spectrometer with the continuous atmospheric pressure interface has the advantages that the requirement of the system on the pumping speed of the vacuum pump can be reduced by using the discontinuous atmospheric pressure interface, so that the size, the weight and the power consumption of the mass spectrometer are reduced. The above experimental results are sufficient to demonstrate the feasibility and effectiveness of a miniature mass spectrometer of the present invention.

It should be noted that the above-mentioned embodiments are only preferred embodiments of the present invention, and the scope of the present invention is not limited thereby, and the present invention may be modified in materials and structures, or replaced with technical equivalents, in the constructions of the above-mentioned various components. Therefore, structural equivalents made by using the description and drawings of the present invention or by directly or indirectly applying to other related arts are also encompassed within the scope of the present invention.

Claims

1. A miniature mass spectrometer, comprising:

a trapping device for trapping and storing ions;

a detector for converting the ions into an electrical signal;

a barometer for monitoring the pressure within the vacuum chamber;

a computer for processing the electrical signal data.

2. The miniature mass spectrometer of claim 1, wherein said circuit controls the timing of mass spectrometry, said timing of mass spectrometry for a cycle comprising the steps of: a first stage in which the valve is closed and the capture device, the mass analyser and the detector are inoperative; in the second stage, the valve is opened and closed for multiple times, ions are guided to enter the trapping device discontinuously for multiple times, at the moment, the trapping device works, ions are trapped and enriched, and the mass analyzer and the detector do not work; a third stage in which the valve is held closed and ions trapped and enriched in the trapping device are transferred to the mass analyser, the mass analyser and the detector operating to obtain an electrical signal reflecting mass spectral data; in the fourth stage, the electric signal is transmitted to the computer after being processed by the circuit, and data processing is carried out by software to obtain a mass spectrogram; wherein the time length of each opening of the valve meets the following conditions: and ensuring that the maximum air pressure monitored by the barometer is within the air pressure range of normal work of the capturing device and the vacuum pump.

3. A miniature mass spectrometer as claimed in claim 1, wherein said ionization source employs any one of: electrospray ionization, nano-spray ionization, atmospheric pressure matrix-assisted laser desorption ionization, atmospheric pressure chemical ionization, desorption electrospray ionization, real-time direct analysis ionization, atmospheric pressure dielectric barrier discharge ionization, atmospheric pressure low-temperature plasma desorption ionization and electrospray-assisted laser desorption ionization.

4. The miniature mass spectrometer of claim 1, wherein said discrete atmospheric pressure interface device further comprises: the pipe is arranged in the valve, the valve is clamped in the middle of the pipe, the first capillary is inserted into the first end of the pipe, the second capillary is inserted into the second end of the pipe, the first capillary and the second capillary are not overlapped with the part clamped by the valve, the first capillary is communicated with the atmospheric pressure, and the second capillary is connected with the inlet of the capturing device.

5. The miniature mass spectrometer of claim 4, wherein said valve is selected from the group consisting of a pinch valve, a needle valve, a flapper valve; the pipe is made of an inert rubber material, the inert rubber material comprises silicon rubber, conductive rubber and anti-static rubber, and the doped material of the conductive rubber and the anti-static rubber is carbon or other conductive metals; the first capillary tube and the second capillary tube are both made of inert metal materials, and the outer diameters of the first capillary tube and the second capillary tube are slightly larger than the inner diameter of the tubes.

6. A miniature mass spectrometer as claimed in claim 1 wherein said trapping means is an ion storage means or mass analyser having ion trapping capabilities of the mass spectrometer.

7. The miniature mass spectrometer of claim 6, wherein said ion storage device is selected from the group consisting of an ion funnel and an electrostatic lens: the mass analyzer is selected from any one of a four-stage ion trap, a rectangular ion trap, a cylindrical ion trap, an ion cyclotron resonance trap and an orbit trap.

8. A miniature mass spectrometer according to claim 1, wherein said trapping means and said mass analyser are located within the same vacuum chamber or within two cascaded vacuum chambers respectively.

9. A miniature mass spectrometer according to claim 8, wherein an ion guide means is provided between two of said vacuum chambers in cascade for guiding ions from said trapping means into said mass analyser, said ion guide means being selected from a sampling cone or an ion guide rod.

10. The miniature mass spectrometer of claim 1, wherein said detector is selected from the group consisting of an electron multiplier, a faraday cup, a photomultiplier, a microchannel plate; the barometer is selected from a pirani vacuum gauge, a thermocouple vacuum gauge, a hot cathode vacuum gauge, and a cold cathode vacuum gauge.